Guided bone regeneration membrane and manufacturing method thereof

ABSTRACT

A guided bone regeneration material is disclosed. The guided bone regeneration material includes biodegradable fibers produced by an electro spinning method. The biodegradable fibers produced by the method include a silicon-releasing calcium carbonate and a biodegradable polymer. The silicon-releasing calcium carbonate is a composite of siloxane and calcium carbonate of vaterite phase. The biodegradable fibers may be coated with apatite. When the guided bone regeneration material is immersed in a neutral aqueous solution, silicon species ions are eluted from the calcium carbonate. The guided bone regeneration material excels in bone reconstruction ability.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part application of U.S. application Ser. No.12/591,258 filed on Nov. 13, 2009, which claims the priority of JapanesePatent Application No. 2007-231621, filed on Sep. 6, 2007. Thedisclosures of these prior applications are incorporated by reference intheir entireties.

FIELD OF THE INVENTION

The present invention relates to a guided bone regeneration material anda manufacturing method thereof. The guided bone regeneration material isused in a guided bone regeneration (GBR) technique which is a techniquefor repairing bone defects and is widely used in the field of oralsurgery and maxillofacial surgery.

RELATED ART OF THE INVENTION

Guided bone regeneration membrane is a masking membrane that covers bonedefect areas so as to prevent invasion of non-osteogenesis-contributingcells and tissues into the bone defect areas and to allow the bone toreconstruct by taking full advantage of the self-regenerative powerthereof. Guided bone regeneration techniques using these membranes cancure bone defects by using a healing potential which the living bodyinherently has. The techniques are not complicated in their operativeprocedures and have given many satisfactory outcomes in oral surgery.

Guided bone regeneration membranes may be broadly grouped undernon-bioresorbable membrane and bioresorbable membrane. Apolytetrafluoroethylene (expanded polytetrafluoroethylene; ePTEF) hasbeen practically used as a material for a non-bioresorbable membrane,from which good clinical data have been obtained. This material,however, places a not-so light burden on a patient, because it is notbioresorbable and thereby needs a secondary operation for the removal ofthe membrane after the target bone defect area is repaired. In addition,it is difficult to adopt this material to a large defect area, becausethe material is bioinert (non-bioresorbable). In contrast, use of guidedbone regeneration membrane that are bioresorbable can avoid the surgicalstress caused by the secondary operation. Exemplary materials for suchbioresorbable guided bone regeneration membrane include poly(lacticacid)s as bioresorbable synthetic polyesters; and copoly(lacticacid/glycolic acid)s; and collagens and fasciae each of biologicalorigin. Such bioresorbable guided bone regeneration membrane have beenrecently investigated and developed heavily, and some of them havealready been commercialized. Typically, there have been proposed a widevariety of guided bone regeneration membrane and manufacturing methodsthereof; such as a bone regeneration membrane including a composite of abioresorbable polymer with tricalcium phosphate or hydroxyapatite andhaving micropores (Japanese Unexamined Patent Application Publication(JP-A) No. H06 (1994)-319794); a protective membrane including a feltmade from a bioresorbable material (Japanese Unexamined PatentApplication Publication (JP-A) No. H07 (1995)-265337; and JapaneseUnexamined Patent Application Publication (JP-A) No. 2004-105754); amultilayer membrane including a sponge-like collagen matrix layer and arelatively impermeable barrier layer (Japanese Unexamined PatentApplication Publication (Translation of PCT Application) (JP-A) No.2001-519210); a bioresorbable tissue regeneration membrane for dentaluse, which has a porous sheet-like structure including a polymer blendcontaining two or more different bioresorbable polymers (JapaneseUnexamined Patent Application Publication (JP-A) No. 2002-85547); aresorbable flexible implant in the form of a continuous micro-poroussheet (Japanese Unexamined Patent Application Publication (Translationof PCT Application) (JP-A) No. 2003-517326); and a biocompatiblemembrane prepared by three-dimensional powder sinter molding throughapplication of laser light to a biodegradable polymer powder (JapaneseUnexamined Patent Application Publication (JP-A) No. 2006-187303).

In particular, oral or maxillary bone defects should be desirably curedas soon as possible, because it is very important to maintain and ensuremastication for the health maintenance in a super-graying society. Toimprove osteogenic ability, there have been attempts to incorporate afactor such as an osteogenesis inducer (Japanese Unexamined PatentApplication Publication (JP-A) No. 1106 (1994)-319794), a growth factoror a bone morphogenic protein (Japanese Unexamined Patent ApplicationPublication (Translation of PCT Application) (JP-A) No. 2001-519210; andJapanese Unexamined Patent Application Publication (JP-A) No.2006-187303) in a bioresorbable membrane. However, it is difficult tohandle these factors. Accordingly, there is a need to develop abioresorbable guided bone regeneration material having superior bonereconstruction ability to allow the bone to self-regenerate morereliably and more rapidly.

In view of recent trends of researches and technologies for bio-relatedmaterials, the main stream of researches has shifted from a materialdesign for the bonding of a material with the bone to a material designfor the regeneration of a real bone. In these researches, the role ofsilicon in osteogenesis has received much attention, and a variety ofmaterials containing silicon have been designed (TSURU Kanji, OGAWATetsuroi, and OGUSHI Hajime, “Recent Trends of Bioceramics Research,Technology and Standardization,” Ceramics Japan, 41, 549-553 (2006)).

For example, it has been reported that the controlled release of siliconcan act on cells to promote osteogenesis (H. Maeda, T. Kasuga, and L. L.Hench, “Preparation of Poly(L-lactic acid)-Polysiloxane-CalciumCarbonate Hybrid Membranes for Guided Bone Regeneration,” Biomaterials,27, 1216-1222 (2006)). Independently, when composites of a poly(lacticacid) with one of three calcium carbonates (calcite, aragonite, andvaterite) are soaked in a simulated body fluid (SBF), the composite of apoly(lactic acid) with vaterite forms a bone-like apatite within ashortest time among the three composites (H. Maeda, T. Kasuga, M.Nogami, and Y Ota, “Preparation of Calcium Carbonate Composite and TheirApatite-Forming Ability in Simulated Body Fluid”, J. Ceram. Soc. Japan,112, S804-808 (2004)).

These findings demonstrate that the use of vaterite which graduallyreleases silicon is believed to be a key to provide a guided boneregeneration material that gives rapid bone reconstruction. Inventors ofthe present invention have already disclosed silicon-releasing calciumcarbonate of vaterite phase and a production method thereof in JPApplication No. 2006-285429 (JP publication No. 2008-1000878).

SUMMARY OF THE INVENTION

An object of the present invention is to provide a bioresorbable guidedbone regeneration material that is capable of effectively inducing abone reconstruction ability. Another object of the present invention isto provide a method for manufacturing a guided bone regenerationmaterial of high performance (achieving rapid bone reconstruction) in aninexpensive and industrially advantageous manner.

The present invention provides, in an embodiment, a fibrous guided boneregeneration material which contains a silicon-releasing calciumcarbonate and a biodegradable polymer, such as poly(lactic acid). Thefibrous material may be coated with an apatite.

The present invention provides, in an embodiment, a fibrous guided boneregeneration material that may have a bi-layered structure, whichincludes a first nonwoven fabric layer and a second nonwoven fabriclayer. The first nonwoven fabric layer contains a silicon-releasingcalcium carbonate and a biodegradable polymer, such as poly(lactic acid)(PLA) as principal components (hereinafter referred to as “Si—CaCO₃/PLAlayer”). The second nonwoven fabric layer contains biodegradablepolymer, such as PLA as a principal component (hereinafter referred toas “PLA layer”). In the bi-layer structured guided bone regenerationmembrane, the PLA layer has the function of preventing the invasion ofsoft tissues, and the apatite-coated Si—CaCO3/PLA layer has the functionof improving cellular affinity and/or osteogenic ability.

In another embodiment, a technique of manufacturing a nonwoven fabricthrough electrospinning is adopted to the manufacturing of such a guidedbone regeneration material. This provides an easy manufacturing of amaterial that has continuous pores for supplying nutrients to cells andshows improved fitting ability to an affected area. Such a bioresorbableapatite that improves cellular initial adhesion can be easily applied tothe fibrous material containing silicon-releasing calcium carbonate andPLA by soaking the fibrous material in a simulated body fluid (SBF).

The guided bone regeneration material according to the present inventionshows high cellular growth ability in cellular affinity tests usingosteoblastic cells (MC3T3-E1 cells) and is expected as a bioresorbableguided bone regeneration material that excels in bone reconstructionability. The method according to the present invention can easily andefficiently manufacture a guided bone regeneration material having theabove possibility.

BRIEF DESCRIPTION OF THE DRAWINGS

Other objects, features and advantages of the present invention will beunderstood more fully from the following detailed description made withreference to the accompanying drawings. In the drawings:

FIG. 1 is a scanning electron micrograph (SEM photograph) of a PLA layersurface of a guided bone regeneration membrane prepared in Example 1;

FIG. 2 is a scanning electron micrograph of a Si—CaCO₃/PLA layer surfaceof the guided bone regeneration membrane prepared in Example 1;

FIG. 3 is a scanning electron micrograph of a surface of a PLA layerprepared in Example 2;

FIG. 4 is a scanning electron micrograph of a surface of a Si—CaCO₃/PLAlayer prepared in Example 2;

FIG. 5 is a scanning electron micrograph of fibers configuring theSi—CaCO₃/PLA layer prepared in Example 2;

FIG. 6 is a scanning electron micrograph of fibers configuring theSi—CaCO₃/PLA layer after soaking a composite membrane prepared inExample 2 in 1.5 SBF;

FIG. 7 depicts X-ray diffraction patterns of the composite membraneprepared in Example 2, before and after soaking in 1.5SBF; and

FIG. 8 is a graph for the evaluation of the cellular affinity of theSi—CaCO₃/PLA layer and PLA layer prepared in Example 2.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Embodiments of the invention relate to bone regeneration materials thatcomprise biodegradable fibers that comprise a biodegradable polymer anda silicon-releasing calcium carbonate. A silicon-releasing calciumcarbonate is a calcium carbonate that contains releasable silicon.Embodiments of the present invention will be further illustrated withthe following examples, with reference to various embodiments in thedrawings. One skilled in the art would appreciate that these examplesare for illustration only and other modifications and variations arepossible without departing from the scope of the invention.

According to a preferred embodiment of the present invention, a guidedbone regeneration material may be manufactured through the steps ofelectrospinning and soaking in a simulated body fluid (SBF). In theelectrospinning step, a positive high voltage may be applied to apolymer solution, and the resulting polymer solution is sprayed asfibers to a negatively charged collector.

To produce biodegradable materials of the present invention, a spinningsolution may be prepared by dissolving a biodegradable polymer in anappropriate solvent, such as poly(lactic acid) in chloroform (CHCl₃) ordichloromethane (DCM). In accordance with embodiments of the invention,a spinning solution may have a poly(lactic acid) concentration of, forexample, from 4 to 12 percent by weight for easy spinning. In thisdescription, any numerical range is meant to include all numberstherebetween, as if all numbers therebetween have been individuallydisclosed. In this connection, the poly(lactic acid) (PLA) preferablymay have a molecular weight of from about 20×10⁴ to about 30×10⁴.However, PLAs with molecular weights outside this range may also beused. To maintain conditions for satisfactory spinning, the spinningsolution may further contain other solvents, such as dimethylformamide(DMF) and/or methanol (CH₃OH) in a selected amount, such as up to about50 percent by weight relative to the amount of CHCl₃ or DCM.

A spinning solution for the formation of a guided bone regeneration(GBR) material of the present invention may be prepared by adding apowder of silicon-releasing calcium material (e.g., calcium carbonate)to the PLA spinning solution. The silicon-releasing calcium carbonatemay be added to the solution such that the content of thesilicon-releasing calcium carbonate may be from 40 to 60 percent byweight. This allows an apatite to deposit efficiently on the electrospunfibers in the SBF soaking step. Alternatively, a spinning solution forthe formation of a guided bone regeneration material may be prepared bykneading a poly(lactic acid) and silicon-releasing calcium carbonate inpredetermined proportions, using a heating kneader to give a composite,followed by dissolving the composite in a solvent.

In a GBR material of the present invention, a silicon-releasing calciumcarbonate to be mixed with PLA may be formed of a composite of siloxaneand calcium carbonate, wherein the calcium carbonate may be of vateritephase. A composite of siloxane and calcium carbonate may be prepared bya carbonation process described in Japanese Patent Application No.2006-285429 (corresponding to Japanese Unexamined Patent ApplicationPublication (JP-A) No. 2008-100878), the disclosure of which isincorporated herein by reference. In the carbonation process, carbondioxide is blown into a suspension prepared by mixing methanol, slakedlime, and an organic silicon compound. Upon stirring the mixture andblowing carbon dioxide, gelation occurs with the suspension. Productmaterial of the gelation of the suspension may be suction filtered anddried to obtain powders of silicon-releasing calcium carbonate.

The powders of silicon-releasing calcium carbonate may be formed ofspherical particles having an average diameter of about 1 μm. A contentof the silicon doped in the calcium carbonate may be adjusted dependingon the amounts and ratios of methanol, slaked lime and an organicsilicon compound in the suspension. Preferably, the silicon content isabout 0.5-5 wt %, more preferably 1-5 wt %, and most preferably about 2wt %.

Upon immersing a silicon-releasing calcium carbonate in a neutralaqueous solution, such as distilled water or a phosphate bufferedsaline, silicon species ions may be separated from the silicon-releasingcalcium carbonate and be eluted into the solution together with calciumions. In this description, silicon-releasing calcium carbonate will besometimes referred to as Si—CaCO₃.

A biodegradable polymer of a guided bone regeneration material of thepresent invention preferably contains a poly(lactic acid) (PLA) byitself or as a copolymer, such as a copolymer of poly (lactic acid) andpoly(glycolic acid) (PGA), i.e., (copoly(lactic acid/glycolic acid)).Examples of other biodegradable polymers usable with embodiments of theinvention may include synthetic polymers such as polyethylene glycols(PEGS), polycaprolactones (PCLs), as well as copolymers among lacticacid, glycolic acid, ethylene glycol, and/or caprolactone; and naturalpolymers such as fibrin, collagens, alginic acids, hyaluronic acids,chitins, and chitosans.

A fibrous material formed of Si—CaCO₃ and PLA may further containinorganic substances that are usable without biological problems.Examples of such inorganic substances include tricalcium phosphate,calcium sulfate, sodium phosphate, sodium hydrogenphosphate, calciumhydrogenphosphate, octacalcium phosphate, tetracalcium phosphate,calcium pyrophosphate, and calcium chloride.

Using an electrospinning apparatus, a spinning solution is charged andsprayed from a nozzle, converted into fibers (thin streams) in anelectric field while evaporating the solvent. The charged fibers arejetted toward a collector connected with a negative electrode to form athin layer of fibers on the collector. A desired guided boneregeneration membrane may be prepared by changing spinning conditions,such as concentrations, solvent types, supply speeds (feed rates) of thespinning solutions, spinning times, applied voltages, and the distancebetween the nozzle and the collector. The prepared nonwoven fabrics maybe pressed so as to be compacted or to have a desired thickness.

A guided bone regeneration membrane having a bi-layered structure may beproduced by spraying a PLA spinning solution to form a PLA layer,followed by spraying a Si—CaCO₃/PLA spinning solution to form aSi—CaCO₃/PLA layer on the PLA layer. Alternatively, a bi-layer structuremay be prepared by producing a PLA nonwoven fabric and a Si—CaCO₃/PLAnonwoven fabric independently, followed by combining the two nonwovenfabrics.

A guided bone regeneration membrane having a bi-layered structure may becut to a desired size and soaked in a simulated body fluid (SBF) or asolution with 1.5 times higher concentration of inorganic ions comparedto SBF (1.5SBF) at about 37° C. for a predetermined time to precipitatean apatite on the Si—CaCO₃/PLA layer. This gives a bioresorbable guidedbone regeneration membrane including a novel mechanism that caneffectively induce the bone reconstruction.

A simulated body fluid (SBF) is an acellular fluid that has inorganicion concentrations similar to those of human extracellular fluid. A SBFmay be used to reproduce formation of apatite on bioactive materials invitro. See, Kukubo et al., “Apatite formation on ceramics, metal, andpolymers induced by a CaO SiO2 based glass in a simulated body fluid,”in Bioceramics, W. Bonfield, G. W. Hastings, and K. E. Tanner, Eds.1991, Buttrworth-Heinemann: Oxford.

The SBF soaking can be performed even after combining (or laminating)the two layers. Even in this case, the apatite does not appreciablydeposit on the PLA layer, but selectively on the Si—CaCO₃/PLA layer.This is because silicon contained in the Si—CaCO₃/PLA layer can inducenucleation of apatite, and the calcium component continues toprecipitate out to increase the degree of supersaturation of apatitearound the nucleation sites. As a result, apatite selectively depositson the surface of the Si—CaCO₃/PLA layer, but not on the surface of thePLA layer, which is hydrophobic and not conducive to the deposition ofapatite.

EXAMPLES Example 1

Manufacturing methods of guided bone regeneration membranes according toembodiments of the present invention will be illustrated with referenceto several examples below. It should be noted, however, that theseexamples are included merely to aid in the understanding of the presentinvention and are not to be construed to limit the scope of the presentinvention.

Raw materials used in the examples are as follows:

-   -   Silicon-releasing calcium carbonate (Si—CaCO₃): Calcium        carbonate of vaterite phase having a silicon content of 2.9 wt %        prepared by using slaked lime (Microstar T; purity 96% or more;        Yabashi Industries Co., Ltd., Japan), methanol (analytical grade        reagent; purity 99.8% or more; Kishida Chemical Co., Ltd.,        Japan), γ-aminopropyltriethoxysilane (TSL 8331; purity 98% or        more; GE Toshiba Silicones Co., Ltd., Japan), and carbon dioxide        gas (high-purity liquefied carbon dioxide gas; purity 99.9%;        Taiyo Kagaku Kogyo K.K.);    -   Poly(lactic acid) (PLA): PURASORB PL Poly(L-lactide), molecular        weight of 20×10⁴ to 30×10⁴, PURAC Biochem;    -   Chloroform (CHCl₃): Analytical grade reagent, purity 99.0% or        more, Kishida Chemical Co., Ltd., Japan;    -   N,N-Dimethylformamide (DMF): Analytical grade reagent, purity        99.5% or more, Kishida Chemical Co., Ltd., Japan.

A PLA spinning solution having a PLA content of 6.8 wt % was prepared bymixing 10 g of PLA, 110 g of CHCl₃, and 27.5 g of DMF. Separately, aSi—CaCO₃/PLA spinning solution having a Si—CaCO₃ content of 7.5 wt % anda PLA content of 5.0 wt % was prepared by mixing 15 g of Si—CaCO₃, 10 gof PLA, 140 g of CHCl₃, and 35 g of DMF. Using the prepared spinningsolutions, a guided bone regeneration membrane having a bi-layeredstructure of nonwoven fabrics was manufactured by electrospinning.

PLA Layer Preparation Conditions

In this example, the spinning solution feed rate is about 0.1 ml/min.,the applied voltage is 15 kV, the distance between the nozzle andcollector is 10 cm. The nozzle laterally moves in a width of 3 to 4 cmat a rate of 15 cm/min, and a conveyor-type collector (conveyor speed: 5to 6 m/min) is used. A spinning time is about 170 minutes.

Si—CaCO₃/PLA Layer Preparation Conditions

In this example, the spinning solution feed rate is about 0.16 ml/min,the applied voltage is 20 kV, the distance between the nozzle andcollector is 10 cm, and the nozzle laterally moves in a width of 3 to 4cm at a rate of 15 cm/min. A conveyor-type collector (conveyor speed: 5to 6 m/min) is used. A spinning time is about 130 minutes.

The microstructure of a PLA layer thus prepared (the side for preventingsoft tissue invasion) is shown in the scanning electron microscope (SEM)photograph of FIG. 1. The microstructure of the Si—CaCO₃/PLA layer (theside for bone regeneration) is shown in the scanning electron micrographof FIG. 2, demonstrating that Si—CaCO₃ particles are attached to the PLAfibers.

Example 2

A spinning solution having a PLA content of 9.0 wt % was prepared bymixing 9 g of PLA and 91 g of CHCl₃. Using this spinning solution, a PLAlayer was prepared by electrospinning.

PLA Layer Preparation Conditions

In this example, the spinning solution feed rate is 0.05 ml/min, theapplied voltage is 20 kV, and the distance between the nozzle andcollector is 15 cm. The nozzle is fixed, so is the plate collector. Thespinning time is 60 minutes.

Separately, PLA and Si—CaCO₃ were kneaded in a heating kneader at 200°C. for 15 minutes to give a Si—CaCO₃/PLA composite containing 60 wt % ofSi—CaCO₃. A spinning solution having a Si—CaCO₃ content of 13.0 wt % anda PLA content of 8.7 wt % was prepared by mixing 25 g of theSi—CaCO₃/PLA composite and 90 g of CHCl₃. Using this spinning solution,a Si—CaCO₃/PLA layer was prepared by electrospinning.

Si—d CaCO₃/PLA Layer Preparation Conditions

In this example, the spinning solution feed rate is 0.05 ml/min, theapplied voltage is 20 kV, and the distance between the nozzle andcollector is 15 cm. A fixed nozzle and a fixed plate collector are used.The spinning time is 30 minutes.

The two nonwoven fabrics prepared by the above procedures were each cutinto a desired size and affixed or combined with each other to form amembrane. To combine two layers to form a membrane, for example, a PLAlayer may be laid over a Si—CaCO₃/PLA layer, and a stainless steel mesh(40-mesh) may be laid over the PLA layer. A plate heated at 150° C. to160° C. may be placed on the stainless steel mesh and pressed under asuitable pressure for about 10 seconds to produce a combined membrane(composite membrane).

The scanning electron micrographs of the PLA layer surface and of theSi—CaCO₃/PLA layer surface are shown in FIG. 3 and FIG. 4, respectively.A scanning electron micrograph of fibers forming the Si—CaCO₃/PLA layeris shown in FIG. 5, demonstrating that Si—CaCO₃ particles are attachedto PLA fibers.

The Si—CaCO₃/PLA layer surface of the resulting composite membrane wasbrought into contact with 1.5SBF at 37° C. for one day. The scanningelectron micrograph of fibers on the side in contact with 1.5SBF isshown in FIG. 6, demonstrating that a substance quite different fromSi—CaCO₃ covers the surface of fibers, as compared to FIG. 5. The X-raydiffraction patterns before and after soaking in 1.5SBF are shown inFIG. 7, indicating that peaks of apatite appear after the soaking. Theseresults indicate that the Si—CaCO₃/PLA layer surface is coated withapatite.

Bone reconstruction ability of a guided bone regeneration material ofthe present invention was evaluated. The evaluation was performed byobserving and comparing the increase of cells per 1 cm² afterinoculation of osteoblastic cells on the apatite-coated Si—CaCO₃/PLAlayer surface (Si-composite), on the PLA layer surface (PLA), or on acontrol (Thermanox: plastic disc for cell culture which has been treatedon its surface), and soaking the surfaces of these into wells which arefilled with culture medium, respectively.

Experimental Conditions

-   -   Cultivation of cells: 24-well plate was used.    -   Cell type: murine osteoblastic cells (MC3T3-E1 cells: Riken        Institute of Physical and Chemical Research) was used.    -   Cellular inoculation number: 1×10⁴ cells/well.    -   Medium: α-MEM (containing 10% fetal bovine serum).    -   Medium exchange: on the day following the inoculation,        thereafter every other day.    -   Cell counting method: The measurement was performed using the        Cell Counting Kit-8 (cellular growth/cellular toxicity        analytical reagent; Dojindo Laboratories) in accordance with the        protocol attached to the reagent.

FIG. 8 shows changes in the number of cells on an apatite-coatedSi—CaCO₃/PLA layer surface (Si-composite), on a PLA layer surface (PLA),and on a control in terms of cells per 1 cm². The data in FIG. 8demonstrate that the surface of the layer incorporating the novelmechanism (Si—CaCO₃) gives significantly higher growth capability ofosteoblasts proliferation than the surface of PLA layer and control.From this result, guided bone regeneration material of the presentinvention is expected to become an excellent bioresorbable GBR materialthat excels in bone reconstruction ability.

While the above description is of the preferred embodiments of thepresent invention, it should be appreciated that the invention may bemodified, altered, or varied without deviating from the scope and fairmeaning of the following claims.

1. A guided bone regeneration material comprising biodegradable fibersproduced by an electrospinning method, the biodegradable fiberscomprising: a silicon-releasing calcium carbonate; and a biodegradablepolymer.
 2. The guided bone regeneration material according to claim 1,wherein the silicon-releasing calcium carbonate comprises a composite ofsiloxane and calcium carbonate of vaterite phase.
 3. The guided boneregeneration material according to claim 1, wherein when immersed in aneutral aqueous solution, silicon species ion is eluted from thesilicon-releasing calcium carbonate.
 4. The guided bone regenerationmembrane according to claim 1, wherein the biodegradable polymercomprises poly(lactic acid).
 5. The guided bone regeneration materialaccording to claim 1, wherein the silicon-releasing calcium carbonate isproduced by a carbonation process in which carbon dioxide is blown intoa suspension prepared by mixing methanol, slaked lime and an organicsilicon compound, and stirring to cause gelation of the suspension. 6.The guided bone regeneration material according to claim 1, wherein thesilicon-releasing calcium carbonate comprises powders of sphericalparticles.
 7. The guided bone regeneration material according to claim1, wherein the biodegradable fibers are coated with an apatite.
 8. Abiodegradable fiber of a guided bone regeneration material produced byan electrospinning process, the biodegradable fiber comprising: asilicon-releasing calcium carbonate; and a biodegradable polymer.
 9. Thebiodegradable fiber according to claim 8, wherein the silicon-releasingcalcium carbonate comprises a composite of siloxane and calciumcarbonate of vaterite phase.
 10. The biodegradable fiber according toclaim 8, wherein the biodegradable polymer comprises polylactic acid).11. The biodegradable fiber according to claim 8, wherein thesilicon-releasing calcium carbonate is produced by a carbonation processin which carbon dioxide is blown into a suspension prepared by mixingmethanol, slaked lime and an organic silicon compound, and stirring tocause a gelation of the suspension.
 12. The biodegradable fiber of aguided bone regeneration material according to claim 8, wherein thesilicon-releasing calcium carbonate comprises powders of sphericalparticles.
 13. The biodegradable fiber of a guided bone regenerationmaterial according to claim 8, wherein upon immersing in a neutralaqueous solution, silicon species ion is eluted from thesilicon-releasing calcium carbonate.
 14. A method for manufacturing aguided bone regeneration material, the method comprising the steps of:mixing a silicon-releasing calcium carbonate with a solution ofbiodegradable polymer to produce a spinning solution; producingbiodegradable fibers from the spinning solution by electrospinning. 15.The method according to claim 14, wherein the biodegradable polymercomprises poly(lactic acid).
 16. The method according to claim 14,wherein the silicon-releasing calcium carbonate is prepared by acarbonation process.